TRANSGENIC ANIMAL MODEL CORE The Transgenic Core works with investigators to generate animal models that will increase our fundamental understanding of cancer and the function of genes in involved in cancer. This Core was established in 1989 and produces transgenic mice and rats, and gene-targeted mice (knockouts) for Cancer Center members. Other services include rederivation of pathogen free mice, and mouse strain cryopreservation and recovery. The Transgenic Core maintains specialized equipment for microinjection, cryopreservation, and mouse embryonic stem (ES) cell culture. The Core maintains and distributes plasmids for transgene or gene targeting vector construction. To maximize gene targeting success, the Core performs quality assurance tests on ES cell lines, feeder cells, and serum for ES cell culture. This is a collaborative Core that combines the expertise of investigators in the molecular biology of the genes they study and the Core's expertise in producing genetically engineered mice with cutting-edge technology. Unique capabilities that set this Core apart are 1) guaranteed production of transgenic mice and rats, 2) routine production of BAG transgenic mice, 3) production of transgenic mice in unique genetic backgrounds, 4) gene targeting in C57BL/6 ES cell lines in addition to 129/Sv ES cells, 5) open access to reagents and equipment, and training in ES cell culture and microinjection methods. Access to the Transgenic Core obviates the need for investigators to devote resources to equipment purchases and personnel time to training in micromanipulation, ES cell culture, and mouse embryo manipulation. Consultation on all aspects of transgenic and ES cell research is provided, from the design of transgenes and conditional targeting vectors to mouse breeding and phenotype analysis. We deliver an average of nine transgenic founder mice and guarantee that at least three founders will be produced for each DNA construct submitted to the Core. The Core electroporates totipotent ES cells with targeting vectors, selects 480 ES cell clones, and provides investigators with ES cell clone DNA to screen for homologous recombination with targeting vectors. We guarantee that ES cell clones with desired genetic changes will be microinjected into at least 50 mouse blastocysts to produce ES cell-mouse chimeras. The efficiency of these procedures meets or exceeds published values in the literature.Based on past use, the projected annual usage by Center members is 50 transgenic mouse orders, 1 transgenic rat order, 40 ES cell-mouse chimera orders, and 12 orders for production of gene targeted ES cells. This is 60-70% of the Core's total university-wide capacity and is consistent with past usage by Center Members. Based on this level of use, recharge rates will be significantly discounted for Center Members.